An anthracycline antineoplastic antibiotic is a potent anticancer antibiotic, and is widely used for treatment of a malignant lymphoma, leukemia, breast cancer, and the like. In many cases, the antibiotic is administered to the patient in the form of, generally, an injectable (injection solution).
Although the injectable of the anthracycline antineoplastic antibiotic can be dissolved in distilled water for injection, the distilled water for injection may possibly irritate the bladder more strongly than a physiological saline. For this reason, in order to reduce the pain from which the patient suffers at the time of injection, such an injectable is often dissolved in a physiological saline and used in a state that each injectable is thus made isotonic with the blood or body fluid. Nevertheless, it is known that the injectable of the anthracycline antineoplastic antibiotic is often formed like a cluster because π electron clouds thereof overlap with each other due to a substance such as a physiological saline carrying an electrical charge. Thus, it takes a longer time to dissolve such an injectable (see Document 1: Q&A of injection drug incompatibility, Jiho Inc., 2006, pp. 61-62).
For this reason, there have been attempted methods for improving the solubility of an anthracycline antineoplastic antibiotic in a physiological saline. For example, adding of an organic solvent such as ethanol at the time of preparing a pharmaceutical preparation is disclosed (see Document 2: Japanese Unexamined Patent Application Publication No. Hei 7-76515). However, such a method is not practiced yet because of a handling problem. Meanwhile, use of methyl p-hydroxybenzoate or the like (parabens) as a cosolubilizing agent with anthracycline glycoside is disclosed (see Document 3: Japanese Unexamined Patent Application Publication No. Sho 61-246129).
When used in an injection solution form, a drug needs to be dissolved in a predetermined solvent. However, drugs differ from each other in physiochemical property; accordingly, depending on the kind of solvent, a drug cannot be dissolved completely in many cases. For this reason, there have been various attempts to dissolve individual drugs by using a solubilizing aid so that the drugs can be rapidly dissolved in their given solvents.
However, even when a drug is successfully dissolved, it is known that the addition of the solubilizing aid, in turn, causes a so-called contraindication that the stability of the drug may be deteriorated, or the injectable may be colored or decomposed. Therefore, it is not easy to find out a specific solubilizing aid compatible with each drug.
For this reason, in order to improve the solubility of various injectables, the use of a solubilizing aid has been examined. For example, an aromatic carboxylic acid is used as a solubilizing aid for amythiamicin that is an anti-bacterial antibiotic (see Document 4: Japanese Unexamined Patent Application Publication No. Hei 9-124503). Moreover, a base such as sodium hydroxide is used as a solubilizing aid for loxoprofen sodium that is an anti-inflammatory drug (see Document 5: International Application Japanese-Phase Publication No. 2004-515526).